Future treatment of nsclc patients with new egfr targeting drugs

S. de Waard (2014) Future treatment of nsclc patients with new egfr targeting drugs. Bachelor's Thesis, Biology.

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Abstract

The treatment of non-small cell lung carcinoma (NSCLC) patients with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI’s), such as gefitinib and erlotinib, was proven to be effective in a subset of patients with a mutated constitutive active EGFR. However, during treatment the cancer cells evolve and develop resistance against these EGFR-TKI’s, causing a major hurdle for successful treatment. A number of mechanisms were identified responsible for this type of EGFR-TKI resistance; the most common are the gatekeeper EGFR-T790M mutation and C-Met amplification. Some patients have NSCLC due to a ROS1 or anaplastic lymphoma kinase (ALK) chromosomal rearrangement while they have the same pathology. The most efficient methods for this identification are fluorescent in situ hybridization’ (FISH) and immuno- histochemistry (IHC). To overcome resistance, new drugs like crizotinib were used to target the C-Met receptor. Furthermore new generation EGFR-TKI’s including afatinib and WZ4002, have been developed. The efficacy of these new drugs was tested in different type of NSCLC cells, in various in vitro and in vivo models. The combination of WZ4002 with crizotinib showed the most dramatic effect against the mutated cells, while the side effects and toxicity were marginal compared to the afatinib and crizotinib combination. Thus, the use of crizotinib and WZ4002 can overcome EGFR-TKI resistance the case of a mutated EGFR.

Item Type:	Thesis (Bachelor's Thesis)
Degree programme:	Biology
Thesis type:	Bachelor's Thesis
Language:	English
Date Deposited:	15 Feb 2018 07:59
Last Modified:	15 Feb 2018 07:59
URI:	https://fse.studenttheses.ub.rug.nl/id/eprint/12176

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